Available cardioplegic solutions and methods for administering cardioplegia are discussed in D. Yu. Romanovsky's paper “The Pathophysiological Evaluation of Methods for Myocardium Protection in Coronary Artery Bypass Surgery with Cardiopulmonary Bypass.”. Extended abstract of Cand. Sci. (Med.), St. Petersburg, 2004 [1]. The author identifies the following basic techniques of cardioplegia:
1. Cold crystalloid cardioplegia (CCC) and hypothermic perfusions. In conducting comparative studies, the author used cold crystalloid cardioplegia (CCC) suggested by B. A. Konstantinov in 1981 and based on a consecutive application of two solution formulations: a high-potassium one for cardiac arrest and a low-potassium one for subsequent perfusions. Among the drawbacks of this method are a need to cool the heart and the whole body and the use of a cardioplegic solution as a blood substitute in the myocardium thus creating a substantial risk of surgical complications.
2. Intermittent warm-blood potassium cardioplegia (IWBPC) and normothermic perfusions. The author carried out his comparative studies based on a cardioplegia delivery procedure earlier described by A. M. Calafiore and coauthors (Calafiore A M, Teodori G, Mezzetti A, Bosco G, Verna A M, Di Giammarco G, et al. Intermittent Antegrade Warm Blood Cardioplegia. Ann Thorac Surg 1995 February; 59:398-402) involving delivery of a 30% pure potassium chloride solution in the blood cardioplegia line. Thus, said method does not require a special cardioplegic solution. The cardioplegic mixture is a combination of blood and potassium chloride. The disadvantage of this method is a high risk of drug dosage and administration time errors. High potassium levels may result in a failure to restore the heart function, while low potassium levels can lead to a sudden resumption of heart beat, exhaustion of energy resources, and, as a consequence, to myocardial ischemia. A further drawback of this method is that the cardioplegic mixture lacks additional agents to protect the myocardium. This may have negative consequences, when during surgery it becomes necessary to interrupt the delivery of cardioplegia for a long time in order to clean the surgical site from blood.
3. Cold blood potassium cardioplegia (CBPC) and normothermic perfusions (“warm body, cold heart”). This method involves using crystalloid cardioplegic solutions mixed with cold blood for infusion in the heart. To conduct comparative studies, the author “proposed and introduced into clinical practice a simple and generally available solution for delivering blood cardioplegia. Said solution is prepared predominantly based on official solutions using minimum components . . . ” Among the drawbacks of this method one should mention its inability to avoid a negative impact of hypothermia on the myocardium, because cold blood stops adequately sustain acid-base and osmotic homeostasis and is unable to penetrate into smallest capillaries due to higher viscosity and interstitial edema.
Further to the above, the following should be noted.
The CCC procedure described in [1], which involves two self-prepared solutions of rather complicated formulations—a high-potassium one for cardiac arrest and a low-potassium one for subsequent perfusions—is rarely used in practice. The reasons are a high labor input required for preparing said solutions and a need to control the quality of resulting drugs. In the majority of cases, cardiac arrest and maintenance of asystole during the CCC procedure are achieved using industrially available crystalloid cardioplegic solutions, for example, Custodiol. For years of application of this procedure, dozens of other formulations for cold cardioplegia have been developed, but the challenge of reducing surgical complications associated with the cooling of the myocardium and the whole body and the use of blood substitute remains pending.
An alternative to cold crystalloid cardioplegia is warm blood cardioplegia, which employs a patient's own warm blood for myocardial protection. However, there are no generally established or commonly obvious technical solutions in this field. Some authors choose to combine cold- and warm-blood cardioplegic procedures. Thus, the use of the IWBPC procedure (potassium chloride injections) [1] carried out without cooling must prevent related complications. However, in the invention RU 2195878 C2 titled Method for Patient Protection in Coronary Artery Bypass Graft Surgery (Oblast Clinical Hospital No 1, Sverdlovsk Oblast) [2], it is suggested to provide an additional protection of the myocardium through cooling it while maintaining a patient's normal body temperature: “The cardioplegic solution is cooled to 6-8° C. and infused into the coronary bed intermittently at 25- to 30-min intervals, while providing additional local cooling of the myocardium by placing sterile crushed ice into the pericardial cavity.” The CBPC procedure described in [1] is based on the application of a crystalloid solution for cold blood cardioplegia, i.e., on mixing cold blood and a blood substitute solution. In hypothermia, blood loses its transport function, as its viscosity and hemoglobin oxygen affinity increase, and that, in the best case, makes its use for cardiac protection impractical or, in the worst case, may cause thrombosis of small capillaries, development of myocardial infarction or a stroke affected by microvasculature paralysis as a result of lactic acidosis and hypoosmotic interstitional cerebral edema with multiple organ failure.
In the paper “Blood Cardioplegia” by Juergen Martin and Christoph Benk, University Hospital Freiburg, Department of Cardiovascular Surgery, MMCTS (Oct. 9, 2006). doi:10.1510/mmcts. 2004.000745 [3], the authors describe various procedures for delivering blood cardioplegia and provide a standard scheme thereof comprising cold induction until complete cardioplegic arrest is achieved, reinfusions of cold blood cardioplegia for 1 min repeated at 20-min intervals, and warm terminal reperfusion prior to releasing the aortic clamp, i.e., when the main phase of the operation is completed. In the paper, mention is made of “continuous warm blood cardioplegia” aimed at preventing any reperfusive myocardial injury prior to the release of the aortic clamp. “However, most surgeons discontinue cardioplegic flow for a few minutes during construction of the distal anastomoses leading to ‘unintentional’ myocardial ischemia. In addition, cardioplegic overdose is a potential problem using this technique.” This explicitly specifies that when applying continuous warm blood cardioplegia prior to the release of the aortic clamp, the authors have no obvious solutions for protecting the myocardium from ischemia, reperfusive damage, and hyperkalemia—the major problems of this method. A similar problem is pointed out in the book by G. E. Morgan and M. S. Mikhail, Clinical Anesthesiology, Book 2 (transl. from English), M.-SPb: BRShOM-Nevsky Dialect Publ., 2000 [4], where they mention about the occasional use of continuous warm blood cardioplegia that may be superior to intermittent hypothermic cardioplegia in respect of myocardial protection, but the unavailability of a bloodless field complicates the surgical procedure and, moreover, normothermic cardiac surgery is performed in the absence of hypothermic protection, especially, with respect to the brain.
Consequently, based on the above-mentioned sources one can conclude that to date the techniques of continuous warm blood cardioplegia have not been adequately elaborated and respective special cardioplegic compositions have not been well enough developed.
The closest analog of this invention is a drug claimed in RF patent 2145843 [5] and meant to be used for continuous blood cardioplegia. Said patent covers two solution types—NCS1 and NCS2 (hereinafter NCS stands for Normothermic Cardioplegic Solution) comprising potassium chloride, magnesium sulfate, tris-(hydroxymethyl)-aminomethane (trometamol), and mannitol. The solutions substantially differ in potassium chloride content: in NCS1 (high potassium solution), the concentration of potassium chloride is 7.0-8.0 g/L; magnesium sulfate, 2.17-2.27 g/L; trometamol, 0.06-0.08 g/L; and mannitol, 28.84-34.09 g/L; while in NCS2 (low potassium solution), the concentration of potassium chloride is 1.91-2.08 g/L; magnesium sulfate, 2.17-2.27 g/L; trometamol, 0.04-0.06 g/L; and mannitol, 44.57-49.83 g/L. According to said patent, NCS1 is used for cardiac arrest and NCS2, to maintain asystole. The procedure described in [5] is as follows: “NCS is continuously mixed with blood from the oxygenator in a ratio of 1:4. After aortic cross clamping, NCS is infused into the heart for 6 minutes. A mixture of NCS1 and blood is infused at a rate of 250-300 mL/min. To maintain asystole, a mixture of NCS2 and blood is infused at a rate of 100-150 mL/min in the same ratio-1:4. Upon completion of the intracardiac phase of the operation, the NCS infusion is stopped.”
It is known from papers that the disadvantage of NCS1 is a risk of complications during cardiac arrest, while the disadvantage of NCS2 is a risk of restarting ventricular (in about 2.5% of patients) and atrial (in about 5% of patients) activities during the operation (L. A. Bokeriya, V. E. Volgushev, R. R. Movsesyan, R. Aibazov, I. I. Berishvili, and I. Yu. Sigaev. Using a Normothermic Cardioplegic Solution in Myocardial Revascularization (in Russian), Grudnaya i Serdechno-Sosudistaya Khirurgiya (Thoracic and Cardiovascular Surgery), No. 4, 2006, p. 5). In addition, the drawback of both NCS1 and NCS2 is a need to make a break for changing the type of solution, which can lead to resumption of cardiac activity and may have an adverse impact on myocardial protection. It should be noted that a need to switch to the other solution may arise not only in the initial phase of cardioplegia when it comes to maintaining asystole but also during the operation in case of spontaneous resumption of cardiac activity. If the bioelectrical activity of the heart resumes during the operation, it is necessary to reinfuse NCS1 and then NCS2 (L. A. Bokeriya, V. A. Lishchuk, I. Yu. Sigaev, M. V. Zatevakhina, D. Sh. Gazizova, L. V. Sadykina, V. E. Volgushev, R. S. Ovchinnikov, A. V. Bulatov, and S. G. Khachatryan. Normothermic Cardiac Surgery. Comparative Analysis of Hemodynamics in Myocardial Revascularization Operations under Hypo- and Normothermia (in Russian). Klinicheskaya Fiziologiya Krovoobrashcheniya (Clinical Physiology of Circulation), 2006, No. 3, p. 63).
The disadvantages of the two solution types are as follows:                Creating a risk of myocardial injury due to a possible erroneous disturbance of the sequence of solutions applied;        Reducing the efficiency of cardioplegia management, which is especially critical in pediatric cardiac operations as well as surgeries on newborn babies and low-weight babies at breast;        Increasing logistic expenses on the acquisition and storage of two types of medicinal products.        
Searching for high-potency cardioplegic solutions enabling a better myocardial protection, expansion of surgical indications, and reduction of cardiac operative mortality with cardiopulmonary bypass using blood cardioplegia, and possessing such features as versatility, simplicity of preparation and use, and commercial availability is one of the focal areas in designing novel cardioplegic solutions.